Abstract
The gut microbiota have been shown to have an important influence, direct and indirect, on the metabolism and toxicity of a wide range of drugs and xenobiotics. The major drug-metabolizing capability of the gut microbiota is reductive metabolism, but demethylation, dehydroxylation, deacylation, decarboxylation, and hydrolysis reactions have also been demonstrated as well as acetylation. Microbiome-driven drug metabolism can result positively in the activation of prodrugs to their pharmacologically active forms or alternatively result in adverse consequences such as toxicity. In addition, the gut microbiota can affect drug metabolism and toxicity indirectly via, e.g., competition of bacterial-derived metabolites for xenobiotic metabolism pathways or the modulation of host metabolic systems.